The Interactive Strategy Training for Active Reading and Thinking (iSTART) game-based intelligent tutoring system (ITS) was developed with a foundation of comprehension theory and principles of learning science to improve students’ comprehension of complex scientific texts. iSTART has been shown to improve reading comprehension for learners from middle school through adulthood, particularly lower knowledge readers, through strategy instruction and game-based practice. This paper describes iSTART, the theoretical foundations that have guided iSTART development, and evidence for the feasibility of game-based practice to improve learning outcomes. This paper also introduces a novel method of assessing students’ reading comprehension through game-based literacy assessments that have been incorporated in iSTART. The development of these stealth assessments was guided by recent work emphasizing the need for rapid, dynamic, and low stakes assessments that evaluate students’ reading skills in the context of brief, dynamic games. Stealth assessments can generate estimates of multiple aspects of students’ reading comprehension quickly and within a motivating environment. The work described in this paper is a promising method to assess students’ literacy in an unobtrusive and authentic way that may lead to improved learning outcomes for students.